Quantitative Model for Gal4p-Mediated Expression of the Galactose/Melibiose Regulon in Saccharomyces cerevisiae

Venkatesh, K. V.; Bhat, Paike Jayadeva; Kumar, Romesh; Doshi, Pankaj

doi:10.1021/bp9801042

Cited by 13 publications

(14 citation statements)

References 22 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Previous modeling work had predicted that the switch response of the network would be unaffected if Gal80p and Gal3p were not autoregulated (16). The results from these studies indicate that at equal levels of the activator and repressor proteins expressed from the tetO 2 promoter under nonrepressing conditions, the galactose network is not inducible.…”

Section: Discussionmentioning

confidence: 74%

“…Modeling has also indicated that the switch is only functional if Gal80p and Gal3p are subject to the same regulation (6). Prior work has demonstrated that the response properties of the system are highly sensitive to relative levels of Gal4p, Gal80p, and Gal3p (16). The Gal2p galactose permease promoter region contains two UASs, whereas the promoter regions for Gal80p and Gal3p contain one UAS.…”

mentioning

confidence: 99%

See 1 more Smart Citation

The Regulatory Roles of the Galactose Permease and Kinase in the Induction Response of the GAL Network in Saccharomyces cerevisiae

Hawkins

Smolke

2006

Journal of Biological Chemistry

View full text Add to dashboard Cite

The GAL genetic switch of Saccharomyces cerevisiae exhibits an ultrasensitive response to the inducer galactose as well as the "allor-none" behavior characteristic of many eukaryotic regulatory networks. We have constructed a strain that allows intermediate levels of gene expression from a tunable GAL1 promoter at both the population and the single cell level by altering the regulation of the galactose permease Gal2p. Similar modifications to other feedback loops regulating the Gal80p repressor and the Gal3p signaling protein did not result in similarly tuned responses, indicating that the level of inducer transport is unique in its ability to control the switch response of the network. In addition, removal of the Gal1p galactokinase from the network resulted in a regimed response due to the dual role of this enzyme in galactose catabolism and transport. These two activities have competing effects on the response of the network to galactose such that the transport effects of Gal1p are dominant at low galactose concentrations, whereas its catabolic effects are dominant at high galactose concentrations. In addition, flow cytometry analysis revealed the unexpected phenomenon of multiple populations in the gal1⌬ strains, which were not present in the isogenic GAL1 background. This result indicates that Gal1p may play a previously undescribed role in the stability of the GAL network response.

show abstract

Section: Discussionmentioning

confidence: 74%

mentioning

confidence: 99%

The Regulatory Roles of the Galactose Permease and Kinase in the Induction Response of the GAL Network in Saccharomyces cerevisiae

Hawkins

Smolke

2006

Journal of Biological Chemistry

View full text Add to dashboard Cite

show abstract

“…Both the ternary and non -ternary scenarios have been previously modelled [35,75] by considering their behaviour at equilibrium. Our model assumes the indirect and nonternary hypothesis , although we do not model the transport of gal80p between the cytoplasm and nucleus.…”

Section: Direct or Indirect Induction?mentioning

confidence: 99%

Evolution of design principles in biochemical networks

et al. 2004

View full text Add to dashboard Cite

Computer modelling and simulation are commonly used to analyse engineered systems.Biological systems differ in that they often can not be accurately characterized, so simulations are far from exact. Nonetheless , we argue in this paper that evolution results in recurring, dynamic organizational principles in biological systems, and that simulation can help to identify them and analyse their dynamic properties. As a specific example, we present a dynamic model of the galactose utilization pathway in yeast, and highlight several features of the model that embody such "design principles".

show abstract

“…Quantification of gene regulatory network is essential for the optimization and operation of bioreactors for the production of foreign proteins. Some of the well‐known examples of genetic regulatory systems that have been explained in quantitative terms are lac operon [13], bacteriophage λ [14], the trp repressor [15] and GLU‐GAL system in yeast [16]. The quantification is typically done by assuming equilibrium between protein–DNA and protein–protein interactions.…”

Section: Introductionmentioning

confidence: 99%

Expression of GAL genes in a mutant strain of Saccharomyces cerevisiae lacking GAL80: quantitative model and experimental verification

Verma

Bhat

Venkatesh

2004

Biotech and App Biochem

View full text Add to dashboard Cite

The regulatory network of GAL genes is a model system for the production of foreign proteins. A mathematical model based on steady state was developed for the expression of GAL (galactosidase) genes in a mutant strain of Saccharomyces cerevisiae lacking GAL80. The transcriptional and translational responses of the GAL switch were predicted at various steady-state glucose concentrations. The model predicted ultrasensitive transcriptional response with a Hill coefficient ( h ) of 1.9 and 3.2 for genes with one and two binding sites respectively. Further, a lesser degree of ultrasensitivity was predicted for translational response with an h value of 1.3 for genes with one binding site and 2.1 for genes with two binding sites. The ultrasensitivity was due to dimerization of regulatory protein Gal4p and co-operative binding of Gal4p to DNA. The steady-state predictions were experimentally verified through measurements of alpha-galactosidase (for one binding site) and beta-galactosidase (for two binding sites). The steady state model was further extended to represent the dynamic expression profile and the same was verified experimentally. The growth phase and the synthesis of foreign protein could be distinctly separated using a mutant strain of Saccharomyces cerevisiae (baker's yeast).

show abstract

Quantitative Model for Gal4p-Mediated Expression of the Galactose/Melibiose Regulon in Saccharomyces cerevisiae

Cited by 13 publications

References 22 publications

The Regulatory Roles of the Galactose Permease and Kinase in the Induction Response of the GAL Network in Saccharomyces cerevisiae

The Regulatory Roles of the Galactose Permease and Kinase in the Induction Response of the GAL Network in Saccharomyces cerevisiae

Evolution of design principles in biochemical networks

Expression of GAL genes in a mutant strain of Saccharomyces cerevisiae lacking GAL80: quantitative model and experimental verification

Contact Info

Product

Resources

About